Fenofibrate pre-treatment suppressed inflammation by activating phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling in renal ischemia-reperfusion injury

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 35; no. 1; pp. 58 - 63
• Main Authors: Yang, Feng-jie, He, Yong-hua, Zhou, Jian-hua
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.02.2015; Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
• Subjects: Animals; Base Sequence; DNA Primers; Enzyme Activation; Fenofibrate - pharmacology; Fenofibrate - therapeutic use; Inflammation - drug therapy; Kidney - blood supply; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Real-Time Polymerase Chain Reaction; Reperfusion Injury - drug therapy; Signal Transduction; Fenofibrate; renal ischemia/reperfusion injury; activating phosphoinositide 3 kinase/protein kinase B; inflammation
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-015-1389-2

Summary The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury (IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: sham-operated group (sham), IRI+saline group (IRI group), IRI+Fenofibrate (FEN) group. Normal saline or Fenofibrate (3 mg/kg) was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α) and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling and peroxisome proliferator-activated receptor-α (PPAR-α) were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.